Effective Mass Spectrometer (MS)-Based Methods for Systematic and Unambiguous Characterization of Protein O-GlcNAcylation

基于有效质谱仪 (MS) 的方法可系统、明确地表征蛋白质 O-GlcNAc 酰化

• 批准号: 2003597
• 负责人: Ronghu Wu
• 金额: $ 41.82万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003597&HistoricalAwards=false
• 关键词: Effective; Mass; Spectrometer; MS; Based

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Ronghu Wu and his group at Georgia Tech are working to improve our ability to characterize an important group of natural protein modifications that involve attachment of sugars. Specifically, Dr. Wu is developing biotechnology tools based on mass spectrometry, in search of better understanding of O-GlcNAcylation, a protein modification which impacts cell function (for example, regulation of gene expression). Graduate and undergraduate students engaged in the research receive valuable training in instrumentation, chemical measurements, and large-scale data analysis. Dr. Wu also provides research opportunities for high school students and teachers, exposing them to cutting-edge research and stimulating their interests in STEM. The Wu group seeks to comprehensively and unambiguously characterize protein O-GlcNAcylation through the development of novel mass spectrometry (MS)-based methods. The problem is challenging because of the low natural abundance of the target proteins in complex biological samples, and the need to distinguish proteins with O-GlcNAc from those with stereoisomeric O-GalNAc. Dr. Wu is developing protocols which selectively enrich O-GlcNAcylated proteins, enabling global and quantitative analysis of protein O-GlcNAcylation. Identification of glycoproteins in the cytosol and the nucleus, and quantification of their dynamics, will provide valuable information to facilitate our understanding of protein O-GlcNAcylation, with potential applications in biological and biomedical research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学测量和成像项目的支持下，格鲁吉亚理工学院的Ronghu Wu教授和他的团队正在努力提高我们表征一组重要的天然蛋白质修饰的能力，这些修饰涉及糖的附着。 具体来说，吴博士正在开发基于质谱的生物技术工具，以更好地了解O-GlcNAcylation，这是一种影响细胞功能（例如，基因表达的调节）的蛋白质修饰。从事研究的研究生和本科生在仪器仪表，化学测量和大规模数据分析方面接受了宝贵的培训。吴博士还为高中学生和教师提供研究机会，让他们接触前沿研究，激发他们对STEM的兴趣。 Wu小组试图通过开发基于质谱（MS）的新方法来全面而明确地表征蛋白质O-GlcNAc化。该问题是具有挑战性的，因为在复杂的生物样品中靶蛋白的天然丰度低，并且需要区分具有O-GlcNAc的蛋白质与具有立体异构体O-GalNAc的蛋白质。Wu博士正在开发选择性富集O-GlcNAc酰化蛋白的方案，从而实现蛋白O-GlcNAc酰化的全局和定量分析。在细胞质和细胞核中的糖蛋白的鉴定，以及它们的动力学的定量，将提供有价值的信息，以促进我们对蛋白质O-GlcNAcylation的理解，在生物学和生物医学研究中具有潜在的应用。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。